tbuckley/cabot-search huggingface dataset:
Treatment outcomes in adults with newly diagnosed B-cell acute lymphoblastic leukemia: A comparison between pediatric-inspired regimens and HyperCVAD at a Hispanic-serving cancer center.
Authors: Shawn Patrick Griffin, Benjamin Lee, Nicholas Pannunzio, Jean Doh, Alexandre Chan, Stefan Ciurea, Deepa Jeyakumar, Susan Mary O'Brien, Angela G Fleischman, Kiran Naqvi, Piyanuch Kongtim
Journal: Journal of Clinical Oncology (2023)

7048 Background: It is unknown if HyperCVAD is more favorable than pediatric-inspired regimens (PIRs) among adult Hispanic patients with newly diagnosed B-cell acute lymphoblastic leukemia. This analysis aims to determine the interaction of Hispanic ethnicity and treatment regimen on outcomes. Methods: Records of adults (≥ 18 years) treated with a PIR or HyperCVAD from January 2011 to November 2022 at our institution were reviewed. Patients were excluded if they received treatment modifications in a clinical trial or were lost to follow-up prior to 6 months. The primary endpoint was event-free survival (EFS) comprised of relapse, death, secondary malignancy, or failure to achieve complete remission. Secondary endpoints included overall survival (OS). Ph+ disease was not grouped into the poor-risk category. Results: 100 patients were included. Median age was 39 years, 57% were male, and 61% self-identified as Hispanic. 48 were included in the PIR and 52 in the HyperCVAD groups. 37 in the PIR group received CALGB 10403. There was no difference in race, ethnicity, rituximab use, WBC, LDH, bone marrow blast %, presence of CNS disease at diagnosis, or poor-risk genetics (Table) between the PIR and HyperCVAD groups. However, a lower rate of Ph+ disease (8.3% vs 58%) and younger median age (31 years vs 49 years) was observed in the PIR group. Allogeneic stem cell transplantation (ASCT) was pursued in 48% of PIR and 37% of HyperCVAD-treated patients. EFS at 5-years was lower among patients receiving a PIR compared to HyperCVAD (28% vs 41%; hazard ratio [HR], 1.89; P = .022). After censoring for ASCT there was no change (P = .03). Treatment group was the only significant predictor for EFS although a treatment-by-subgroup interaction (P &lt; .10) with Hispanic ethnicity was found. OS at 5-years was 61% in PIR and 64% in HyperCVAD-treated patients (HR, 1.54; P = .25). In multivariable Cox regression analysis, Hispanic ethnicity (HR, 2.56; P = .041) and male sex (HR, 2.62; P = .027) were predictors for worse OS. Hispanic patients demonstrated worse EFS with a PIR compared to HyperCVAD (HR, 2.52; P = .008), which remained significant when evaluating only Ph- patients (HR, 2.20; P=.048). Non-Hispanics did not experience the same difference in EFS (HR, 0.88; P=.81). Conclusions: Treatment with a PIR resulted in worse EFS over HyperCVAD in adult Hispanic ALL patients. Future studies focusing on regimen intensity, adherence, and toxicities are needed to explore potential causes for this disparity. [Table: see text]
Real-world data from a multi-center study: Insights to the efficacy and safety in patients with ovarian cancer (OC) received niraparib as first-line (1st-L) maintenance therapy (MT).
Authors: Minmin Zhao, Yang Shen, Ying Zhou, Bingwei Chen, Xin Wu, Pengcheng Miao, Zhi Jiang, Tao Zhu, Xizhong Xu, Bei Zhang, Donglan Yuan, Yang Zhang, Wei Sun, Aiqin He, Min Zhao, Wenjie Hou, Zhuyan Shao, Meiqun Jia, Yanling Zhu, Jun Chen
Journal: Journal of Clinical Oncology (2023)

5551 Background: Niraparib has significantly extended PFS as 1st-L MT OC in PRIMA/PRIME. Due to the more complex in treatment and status of the patients (pts) in clinal practice, more real-world data is needed to verify the efficacy and safety of Niraparib. Meanwhile, exploring the link between clinical characters and PFS, may to establish a clinical model to predict Niraparib benefits. Methods: This is a retrospective multicentric study recruiting OC pts received Niraparib as 1st-L MT from fourteen hospitals throughout China from Jan. 2019 to Dec. 2021. The database lock-time was on Dec. 31st, 2022. The pts’ basic characters, especially biomarkers, KELIM scores, etc. were recorded. Survival analyses were conducted using the Kaplan-Meier method and log-rank test, and 95% CI were calculated. The primary endpoint was PFS, and secondary endpoints included time to treatment discontinuation (TTD), time to first subsequent therapy (TFST) and safety. The exploratory endpoint was to establish a clinical prediction model of Niraparib benefits. Results: 199 pts’ data were analyzed. The median(m) follow-up at the time of the data cutoff was 14.93 months (mos) (12.17, 39.47). Baseline characteristics were shown in Table. MPFS was not reached (NR) (29.80 to not be estimated, NE), with maturity 29.64%, and PFS rate at 6, 12, 18, 24mos was 89.4%, 79.5%, 68.3%, 64.5% respectively, showing the efficacy of Niraparib. MPFS (95% CI) in subgroups were as follows: BRCAwt 23.83mos (23.83 to NE); HRD negative 15.63mos (12.6 to NE); KELIM＜1 NR (15.33 to NE); BRCA1/2m, HRD positive and KEILM≥1 subgroups were all NR yet, due to the no longer enough follow-up time and low data maturity. Multivariate analysis found that pts with &lt;65 years, BRCA1/2m, HRD positive, KELIM＞1, and R0 after primary cytoreductive surgery were likely to have longer PFS. The rate of grade ≥3 thrombocytopenia was 19.1%. Treatment discontinuation occurred in 11 (5.5%) pts due to TEAEs. The clinical prediction model for probability of progression was established from 149 pts (training dataset): Score = 0.612 Age ＞65 + 0.3889 BMI ≤23.90 + 0.097 FIGO IV + 0.191Chronic N +1.398 Surgery result R1/R2 +2.552 BRCA wt . The probability of disease progression received Niraparib in 6, 12 and 18m can be obtained by mapping the score to the nomogram. Conclusions: The efficacy and safety of Niraparib in this study are consistent with the results in PRIME. The clinical predictive model established in this database needs more data to be matured and verified. [Table: see text]
A phase I study of MEK inhibitor selumetinib in combination with azacitidine in patients with higher-risk chronic myeloid neoplasia.
Authors: Gregory Roloff, Anand Ashwin Patel, Kristen M Pettit, Michael J. Thirman, Richard A. Larson, Mariam Nawas, Satyajit Kosuri, Michael William Drazer, Noreen Fulton, Howard Weiner, Wendy Stock, Hongtao Liu, Olatoyosi Odenike
Journal: Journal of Clinical Oncology (2023)

TPS7084 Background: Myelodysplastic syndrome (MDS), Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), and MDS/MPN overlap syndromes present significant clinical challenges for patients deemed transplant ineligible, and who are relapsed or refractory to conventional therapies. RAS-pathway activating mutations in myeloid malignancies are associated with a proliferative phenotype and contribute to disease progression. Cooperation between RAS-dependent signaling and epigenetic dysregulation provides the basis for rationally designed combination studies. Selumetinib (AZD6244) is a potent, selective, orally bioavailable, and non-ATP competitive small molecule inhibitor of MEK1/2, downstream of RAS. Methods: This is an investigator-initiated, Phase I, open-label dose-escalation study of selumetinib in combination with azacitidine for patients with higher risk MDS, MDS/MPNs, and myelofibrosis. The trial will enroll patients with high-risk myeloid neoplasms that meet disease-specific criteria for MDS or MPNs and who require treatment. This phase I study follows a 3+3 dose-escalation design, with three planned dose levels across two different cohorts (A and B). The dose of azacitidine 75 mg/m 2 will remain stable, with three planned selumetinib dose levels (50 mg, 75 mg, and 100mg, respectively) across the two cohorts. Azacitidine will be given on days 1-7 followed by selumetinib from days 7-21 of 28 day cycles. Cohort A includes subjects with MDS with relapsed/refractory disease requiring therapy and MDS/MPN overlap syndromes; Cohort B includes subjects with myelofibrosis refractory or intolerant to JAK inhibitor therapy or ineligible for ruxolitinib treatment given baseline cytopenias (thrombocytopenia &lt; 50,000/uL, anemia &lt; 9 g/dL, and/or red cell transfusion dependent). The trial has an enrollment goal of 18 to 24 subjects, and treatment will continue indefinitely if the patient continues to derive benefit. Dose escalation will proceed independently within both cohorts. Cohort A is nearing completion of enrollment and cohort B is actively enrolling. The primary objective is to determine the maximum tolerated dose of selumetinib in combination with azacitidine. Select secondary and exploratory objectives include describing the preliminary clinical response rates and observing relationships between the presence of RAS activating mutations, RAS pathway activation, and clinical response. Clinical trial information: NCT03326310 .
Racial disparities in hospitalization outcomes among patients with cholangiocarcinoma.
Authors: Inimfon Jackson, Gogo-Ogute Ibodeng, Geneva Guarin, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2023)

6631 Background: Studies have reported on the rising incidence and mortality outcomes among patients diagnosed with cholangiocarcinoma (CCA) but racial disparities in outcomes among inpatients have not been explored in this population. We examined the racial disparities in outcomes among adult hospitalized patients with a diagnosis of CCA. Methods: Retrospective cohort analyses were conducted using data from the National Inpatient Sample (NIS), 2016-2020. Multivariate logistic and linear regression models were used to examine the association between race/ethnicity and patient disposition, length of stay, elective admissions, and total hospital charges. Results: In the adjusted analyses, while Black patients had 14% higher odds (95% Confidence Interval (CI): 1.04–1.25) of being discharged to a facility/home with home health care versus routine discharge when compared to their White counterparts, Hispanics had 14% lower odds (95% CI: 0.79–0.95). Black patients had 39% higher risk (95% CI: 1.19–1.63) of death versus routine discharge relative to the White patients. Compared to White patients, Blacks (AOR: 1.23; 95% CI: 1.13–1.34), Hispanics (AOR: 1.15; 1.06–1.25) and other race/ethnicities (AOR: 1.20; 1.10–1.31) were more likely to have a length of hospital stay greater than 5 days relative to 5 days or less. Hispanics (β: $16,789; 95% CI: $11,480–$22,099) were found to have higher total hospital charges when compared to the White CCA patients. Additionally, Black (AOR: 0.68; 95% CI: 0.60–0.78) and Hispanic patients (AOR: 0.87; 95% CI: 0.77–0.99) were less likely to be admitted electively to the hospital. Conclusions: Despite advances made in treatment of patients with CCA, the prognosis remains poor. We report disparities in various hospitalization outcomes among adult patients with a diagnosis of CCA. Health care providers need to be aware that these disparities exist and health policies should be implemented to narrow the gap in existing disparities. [Table: see text]
Impact of ethnicity and insurance on adverse effects and treatment outcomes related to immune checkpoint inhibitors at a safety net hospital.
Authors: Himil Mahadevia, Benjamin Eidenschink, Stephanie Sarita Harry, Lara Ann Kujtan
Journal: Journal of Clinical Oncology (2023)

e18538 Background: Clinical trials have shown efficacy and safety of immune checkpoint inhibitors (ICI) in the treatment of various malignancies. However, trial populations often do not adequately represent patient populations in the real-world. We report immune related adverse effects (IRAEs) among patients with various malignancies, diverse ethnicities, and government sponsored insurance or uninsured, as well as treatment outcomes of ICIs in metastatic non-small cell lung cancer (mNSCLC). Methods: A retrospective study of adult patients with malignancy, who received ICI or ICI plus chemotherapy from January 1, 2015 to January 1, 2020 was conducted at a safety net hospital. Data was collected from electronic medical records with IRB approval. IRAEs were identified and categorized according to CTCAE v5.0. 1-year overall survival (OS) and median duration of ICI therapy (mDT) were calculated for mNSCLC patients. Results: We reviewed 121 patients: 49% were African American (AA), 40% were white and 11% were other ethnicities. Medicaid/Medicare (M/M) was the primary insurance for 83% of patients, 6% had commercial insurance and 11% were uninsured. The median duration of follow-up was two years. IRAEs occurred in 37% of patients; hypothyroidism was the most common (7.5%), and none led to death. The incidence of grade 2 or higher IRAEs was lower in AA (25.4%) compared to in whites (32.6%), with treatment discontinuation rates of 5% in AA versus 16% in whites. Among mNSCLC patients, AA and other ethnicities had a decreased 1-year OS of 37% and 22% respectively, compared to 48% in whites. The mDT was 8.3 months for AA and 3 months for other ethnicities, compared to 13.2 months for whites. 40% of M/M patients with mNSCLC were alive at 1 year; none of the uninsured patients were alive at 1 year. The mDT was higher in M/M patients (6 months) than uninsured patients (3.5 months). Conclusions: Ethnicity and insurance coverage may influence the incidence of IRAEs and treatment outcomes with ICI. AA had a lower incidence of IRAEs compared to whites. However, minority populations with mNSCLC had decreased survival compared to whites. mNSCLC patients with M/M had better OS than uninsured patients. Minorities and uninsured patients spent less time on ICI compared to other patients. IRAEs are a significant burden and further study of the use of ICIs in diverse populations is warranted.[Table: see text]
GCIG SB-001/NSGO-CTU-PEACE/ANZGOG 1923/2020: Palliation in gynae-oncology—Patients' expectations and assessment of care.
Authors: Kristina Lindemann, Heidi Liland, Mia Sejer Donner, Sue Brew, Yeh Chen Lee, Ingvild Vistad, Elisabeth Berge Nilsen, Janine Margaret Lombard, Mansoor Raza Mirza, Kristine Madsen, Anne Marie Hansson, John Andrews, Rachel Campbell, Alison J. Davis
Journal: Journal of Clinical Oncology (2023)

TPS5635 Background: Patients with advanced gynaecological cancers who are approaching end of life (EOL) have a high symptom burden and following several prior lines of therapy, a low likelihood of response to further anti-cancer treatment. Despite this, 20-30% of women with gynecological cancer received chemotherapy in the last 30 days of life, with potentially detrimental effects on health and quality of life. Little is known about patients' and carers' perceptions and preferences in this phase of illness. Eliciting patient’s values and preferences for EOL care and shared decision-making are central elements of GCIG SB-001/NSGO-CTU-PEACE with the aim of improving patient-centered EOL care. The primary aim of PEACE is to assess the feasibility of collecting data on patient satisfaction towards EOL. Secondary aims include collecting data on patient and carer satisfaction with care, as well as prospective collection of details of their care. Methods: PEACE will prospectively enroll patients in Norway and Australia. Key eligibility criteria include: Patients with gynaecological cancer at an advanced stage with a predicted life expectancy of approximately 4 months. Patients may be on anti-cancer treatment or may be under observation/palliative care. In addition, the patient must be able (both physically and cognitively) to complete patient-reported outcome measures independently. The study will also include an appointed carer (not mandatory). Patient and carer satisfaction with care and the importance of domains of care will be assessed with the CANHELP-Lite individualized (Canadian Health Care Evaluation Project) instrument and FACIT (Functional Assessment of Chronic Illness Therapy). Carer’s perception of the bereavement period and the quality of the patient’s death will be assessed with the CANHELP lite bereavement and the Quality of Death and Dying questionnaire. The study will prospectively collect data on EOL treatment. Patient and carer satisfaction with care and quality of the dying process will be summarized by standard descriptive statistical measures. A sample size of 65 patients would have at least 80% power with 95% confidence to rule out a 60% completion rate in favour of the more interesting 75% rate. Assuming a 10% drop-out rate, PEACE will enrol 73 patients. Enrolment commenced in December 2022. ClinicalTrials.gov Identifier: NCT05142150 Clinical trial information: NCT05142150 .
The smart options of induction therapy for locally advanced betel-nuts related HNSCC in Taiwan.
Authors: Jo-Pai Chen, Wei-Chen Lu, Keng-Man Chiang, Hsing-wu Chen, Huai-Cheng Huang, Chen-Han Chang, Sung-Hsin Kuo
Journal: Journal of Clinical Oncology (2023)

e18080 Background: The treatment of HNSCC in Taiwan is still very challenging and might be related to betel-nuts use. Betel nut chewing might contribute to strong angiogenesis/invasion and treatment refractoriness. In western countries where HPV+ oropharyngeal cancer prevalence is high, induction TPF (TAX323/324) response rate in locally advanced HNSCC is around 70%; Erbitux and TP (Argiris in JCO2008) induction response rate is 86%. In the analysis from KGMH in Taiwan, induction chemotherapy response for locally advanced HNSCC was 55% in betel-nuts chewers compared with 75% in non-users ( p=0.038; From Su in World Journal of Surgical Oncology 2016). In further studies from Taiwan, Avastin-PF induction benefit (ORR 80%) was also prominent from NTUH (Huang in ESMO Asia2016); Erbitux-TPF induction response rate was 88% from VGH by Lu in Head &amp; Neck2019. Neoadjuvant biochemotherapy seemed to bring more benefits in betel-nuts related HNSCC. In the era of incorporating immunotherapy to neoadjuvant setting of HNSCC, triple therapy of bio-chemoimmunotherapy deserves more attention. Methods: From 2012 to 2022, 111 unresectable stage IVA &amp; IVB betal-nuts related HNSCC patients (OSCC 69, Hypopharynx 26, OPC 13) had ever received induction Bio-chemotherapy or triple therapy (Bio-chemoimmunotherapy) in Yun-lin Branch of National Taiwan University Hospital. We have reviewed basic characteristics, therapeutic regimens, induction response, and final outcomes of these patients. Results: See table. Conclusions: Induction TPF response in locally advanced betel-nuts related HNSCC in Taiwan was not so prominent. Flexible chemotherapy backbones, such as TP/DP-HDFL(weekly docetaxel or paclitaxel with cisplatin and 24-hr high dose 5-fluorouracil/leucovorin infusion), might produce acceptable response rates with less toxicity. Bio(EGFR or VEGFR-targeting)-chemotherapy or Bio-chemoimmunotherapy has brought encouraging induction response with favorable toxicity profiles to conversion surgery or definite CCRT. Further investigation and clinical trials will be urgently warranted. [Table: see text]
GLORIOSA: A randomized, open-label, phase 3 study of mirvetuximab soravtansine with bevacizumab vs. bevacizumab as maintenance in platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.
Authors: David M. O'Malley, Tashanna K. N. Myers, Claudio Zamagni, Elisabeth Diver, Domenica Lorusso
Journal: Journal of Clinical Oncology (2023)

TPS5622 Background: Elevated folate receptor-alpha (FRα) expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing a rational target for antibody drug conjugate (ADC) development in ovarian cancer. Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has received accelerated approval for patients with FRα positive platinum resistant ovarian cancer. MIRV in combination with BEV has demonstrated clinically meaningful activity, along with acceptable tolerability, in patients with FRα expressing ovarian cancer. 1 Methods: GLORIOSA is a randomized, open-label, phase 3 study designed to evaluate the efficacy of in combination with bevacizumab compared with bevacizumab alone as maintenance for patients with FRα-positive recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancers who have not progressed after second line platinum-based chemotherapy plus bevacizumab (which may be given on protocol for patients with high FRα tumor expression). Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1 CDx Assay (high expression; ≥ 75% of viable tumor cells staining at 2+ intensity) and 1 prior line of therapy is required for inclusion. GLORIOSA is designed to randomize 418 patients, 1:1 receiving intravenous MIRV at a dose of 6 mg/kg adjusted ideal body weight plus bevacizumab 15mg/kg every 3 weeks or receiving bevacizumab 15mg/kg every 3 weeks until disease progression or unacceptable toxicity. Radiological assessments will be conducted every 9 weeks (± 2 weeks) for 72 weeks, and subsequently every 18 weeks (± 3 weeks) until progressive disease (PD), death, the start of new anticancer therapy, or withdrawal of consent from the study (whichever occurs first). The primary efficacy endpoint is progression-free survival by investigator and will also be assessed as a sensitivity analysis. The secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. GLORIOSA is a global study that opened for enrollment in December 2022. Reference: 1. Gilbert L, Oaknin A, Matulonis UA, et al. Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol. 2023; 170: 241–247 Clinical trial information: NCT05445778 .